The Prostate Cancer Program (05) has 3 central themes: 1) mechanisms of castration resistance; 2) molecular targeting; and 3) translational studies, both clinical and preclinical. The major program emphasis is on the study of the mechanisms of aberrant androgen receptor (AR) activation in the development of castration resistant prostate cancer (CRPC). Studies to understand the function and regulation of AR divide into 3 areas: a) regulation of intracrine androgens, b) aberrant AR activation, and c) the role of co-regulators. Molecular targeting of CRPC focuses on the role of neuropeptides, kinase inhibitors, and the role of autophagy. In translational studies, eight different targets are under investigation, four of which have progressed to investigator-initiated clinical trials. Our long-term goal is to develop mechanism-based treatments for CRPC and castration-adjunctive therapy that may lead to a more effective intervention than castration alone. The program has 17 members from 8 different departments and divisions. It has 8 NCl-funded projects for $1.1 million ADC (total peer-reviewed funding, $3.1 million ADC). The group has 320 publications; 54% are inter-programmatic and 26% are intra-programmatic